Acromegaly occurs due to excessive action of insulin-like growth factor I (IGF-I) after the growth plate cartilage fuses in adulthood.
It can be an insidious disease. Symptoms, which may precede diagnosis by several years, can be divided into the following groups:
1. Symptoms due to local mass effects of an intracranial tumour
Tumour damage to the pituitary stalk may cause hyperprolactinemia (Increased blood prolactin levels associated with galactorrhoea) due to loss of inhibitory regulation of prolactin secretion by the hypothalamus
2. Symptoms due to excess of GH/IGF-I including:
– Hyperhidrosis (Not hypohidrosis)
– Arthritis
– Peripheral Neuropathies e.g. Carpal Tunnel Syndrome

This patient has hypercalcaemia due to hyperparathyroidism. However, the intestinal absorption of calcium is mainly controlled by 1,25 dihydroxy-vitamin D. Under the influence of calcitriol (active form of vitamin D), intestinal epithelial cells increase their synthesis of calbindin (calcium-binding carrier protein) necessary for active calcium ion absorption.

The use of hormone replacement therapy (HRT) based on unopposed oestrogen increases the risk of endometrial cancer, and uterine hyperplasia or cancer.
Evidence from randomized controlled studies showed a definite association between HRT and uterine hyperplasia and cancer. HRT based on unopposed oestrogen is associated with this observed risk, which is unlike the increased risk of breast cancer linked with combined rather than unopposed HRT.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
– Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
– Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney
This patient has the central type from metastases.
In patients with central DI, desmopressin is the drug of choice. It is a synthetic analogue of antidiuretic hormone (ADH). It is available in subcutaneous, IV, intranasal, and oral preparations. Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended during the initial phase of treatment.

Several dipeptidyl peptidase-4 (DPP-4) inhibitors are in clinical development; these are orally active and increase levels of active glucagon-like peptide-1 (GLP-1), which in turn increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels.
Sitagliptin and vildagliptin both have a long duration of action, allowing once-daily administration. Both sitagliptin and vildagliptin are safe and tolerable with a low risk of hypoglycaemia. In drug-naïve subjects with type 2 diabetes, both sitagliptin and vildagliptin reduce A1C levels by ,1% as monotherapy.

Prolactinomas, benign lesions that produce the hormone prolactin, are the most common hormone-secreting pituitary tumours.
Based on its size, a prolactinoma can be classified as a microprolactinoma (< 10 mm diameter) or a macroprolactinoma (>10 mm diameter). If the prolactinoma is large enough to compress the surrounding normal hormone-secreting pituitary cells, it may result in deficiencies of one or more hormones (e.g., thyroid-stimulating hormone [TSH], growth hormone [GH], adrenocorticotropic hormone). However, the patient has microadenoma so it is unlikely to cause compression manifestations.
Hyperprolactinemia inhibits GnRH secretion from the medial basal hypothalamus and LH release from the pituitary.

Primary hyperaldosteronism, also known as Conn’s Syndrome, is one of the most common causes of secondary hypertension (HTN).
The common clinical scenarios in which the possibility of primary hyperaldosteronism should be considered include the following:
– Patients with spontaneous or unprovoked hypokalaemia, especially if the patient is also hypertensive
– Patients who develop severe and/or persistent hypokalaemia in the setting of low to moderate doses of potassium-wasting diuretics
– Patients with treatment-refractory/-resistant hypertension (HTN)
Patients with severe hypokalaemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalaemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs.

This patient has polycystic ovarian syndrome (PCOS). Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.
First-line medical therapy usually consists of an oral contraceptive to induce regular menses. The contraceptive not only inhibits ovarian androgen production but also increases sex hormone-binding globulin (SHBG) production. The American College of Obstetricians and Gynaecologists (ACOG) recommends the use of combination low-dose hormonal contraceptive agents for long-term management of menstrual dysfunction.
If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. Pregnancy should be excluded before therapy with oral contraceptives or androgen-blocking agents are started.
First-line treatment for ovulation induction when fertility is desired is clomiphene citrate. Second-line strategies may be equally effective in infertile women with clomiphene citrate–resistant PCOS.

The patient is most likely to have Addison’s disease as he has a history of autoimmune disease, hyperkalaemia and hypotension.
It is important to keep an Addisonian crisis on the differential in cases of shock, especially since adrenal crisis can be the patient’s first presentation of adrenal insufficiency.
Patients with Addison’s disease are prone to developing hypoglycaemia due to loss of the glucogenic effect of glucocorticoids. Given the sudden deterioration, a glucose level must be checked.

Paget disease is a localized disorder of bone remodelling that typically begins with excessive bone resorption followed by an increase in bone formation. This osteoclastic over activity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.
Approximately 70-90% of persons with Paget disease are asymptomatic; however, a minority of affected individuals experience various symptoms, including the following:
– Bone pain (the most common symptom)
– Secondary osteoarthritis (when Paget disease occurs around a joint)
– Bony deformity (most commonly bowing of an extremity)
– Excessive warmth (due to hypervascularity)
– Neurologic complications (caused by the compression of neural tissues)
Measurement of serum alkaline phosphatase—in some cases, bone-specific alkaline phosphatase (BSAP)—can be useful in the diagnosis of Paget disease. Elevated levels of urinary markers, including hydroxyproline, deoxypyridinoline, C-telopeptide, and N -telopeptide, may help identify patients with Paget disease.
Serum calcium and phosphate levels should be within the reference range in patients with Paget disease.